Synthesis,in-vitro α-glucosidase inhibition,antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives |
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| Institution: | 1. Department of Chemistry, Karnatak University, Dharwad 580003, India;2. Department of Chemistry, Jain College of Engineering, Belagavi 590014, India;1. Laboratory of Analytical Chemistry and Bromatology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco;2. Laboratory of Pharmacology and Toxicology, Biopharmaceutical and toxicological analysis research team, Faculty of Medicine and Pharmacy Mohammed V University in Rabat, Morocco;3. Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;4. Science Faculty, Department of Chemistry, Cumhuriyet University, Sivas 58140, Turkey;5. Laboratoire de Chimie Appliquée et Environnement (LCAE), Faculté des Sciences, Université Mohammed I, 60000 Oujda, Morocco;6. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt;7. Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 61421, P. O. Box 960, 61421, Saudi Arabia;8. Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco;9. Institute of Condensed Matter and Nanosciences, Molecular Chemistry, Materials and Catalysis (IMCN/MOST), Université catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium |
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| Abstract: | α-Glucosidase is considered as a therapeutic target for the treatment of type 2 diabetes mellitus (DM2). In current study, we synthesized pyrrolidine-2,5-dione (succinimide) and thiazolidine-2,4-dione derivatives and evaluated for their ability to inhibit α-Glucosidase. Pyrrolidine-2,5-dione derivatives (11a–o) showed moderate to poor α-glucosidase inhibition. Compound 11o with the IC50 value of 28.3 ± 0.28 µM emerged as a good inhibitor of α-glucosidase. Thiazolidine-2,4-dione and dihydropyrimidine (TZD-DHPM) hybrids (22a–c) showed excellent inhibitory activities. The most active compound 22a displayed IC50 value of 0.98 ± 0.008 µM. Other two compounds of this series also showed activity in low micromolar range. The in-vivo antidiabetic study of three compounds 11n, 11o and 22a were also determined using alloxan induced diabetes mice model. Compounds 11o and 22a showed significant hypoglycemic effect compared to the reference drug. In-vivo acute toxicity study showed the safety of these selected compounds. In-silico docking studies were carried out to rationalize the in-vitro results. The binding modes and bioassay results of TZD-DHPM hybrids showed that interactions with important residues appeared significant for high potency. |
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| Keywords: | Pyrrolidine-2 5-dione Succinimide Cyanoacetate Thiazolidine-2 4-dione α-Glucosidase |
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